Pancreatic neuroendocrine tumors

Muniraj, Thiruvengadam; Vignesh, S Bala; Shetty, Shilpa; Thiruvengadam, Sudha; Aslanian, Harry R.

doi:10.1016/j.disamonth.2012.10.002

Cited by 25 publications

(17 citation statements)

References 96 publications

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“…Clinical presentation and symptoms correlate with the functionality of the tumor and the type of hormones that are overexpressed. Among this type of malignancy, insulin-secreting pancreatic neuroendocrine tumors are the most common, followed by gastrinomas, glucagonoma, vasoactive intestinal peptide secreting tumors (VIPomas), and somatostatinomas 33. PTH-secreting pancreatic neuroendocrine tumors are rare, with the present case being only the third reported in the literature to date.…”

Section: Discussionmentioning

confidence: 65%

An unusual case of malignancy-related hypercalcemia

Doyle¹,

Malcolm²

2013

IJGM

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Objective To report the case of a 28-year-old woman who presented with hypercalcemia (total calcium =4.11 mmol/L), elevated parathyroid hormone (PTH) 24.6 pmol/L, normal parathyroid hormone-related peptide 7.8 pg/mL, and a 63 mm × 57 mm, poorly differentiated neuroendocrine carcinoma (small-cell type) pancreatic mass with liver metastases. Investigations and treatment Hypercalcemia was acutely managed with intravenous fluids, pamidronate and calcitonin. Investigations for multiple endocrine neoplasia type 1 and parathyroid adenoma were initiated. The identified neuroendocrine tumor was treated with cisplatinum/etoposide chemotherapy. Results The pancreatic mass (56 mm × 49 mm) and metastases decreased in size with chemotherapy and calcium levels normalized. Eight months later, calcium increased to 3.23 mmol/L, PTH increased to 48.2 pmol/L, and the pancreatic mass increased in size to 67 mm × 58 mm. The patient was given a trial of cinacalcet but was unable to tolerate it. Chemotherapy was restarted and resulted in a decrease in the pancreatic mass (49 mm × 42 mm), a reduction in PTH levels (16.6 pmol/L), and calcium levels (2.34 mmol/L). Conclusion Ectopic PTH secreting tumors should be considered when there is no parathyroid related cause for an elevated PTH. Recognizing the association between PTH and hypercalcemia of malignancy may lead to an earlier detection of an undiagnosed malignancy.

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Section: Discussionmentioning

confidence: 65%

An unusual case of malignancy-related hypercalcemia

Doyle¹,

Malcolm²

2013

IJGM

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“…There is no sufficient data demonstrating the superiority of any of these methods to one another. 16 In a review published in 2009, the 5-year survival rates were 40 to 67% and 50 to 65% in single embolization and chemoembolization, respectively. 42 In a series including 148 patients who were treated with radioembolization (Yttrium-90 resin microspheres) the median survival time was 70 months, the rate of complete response was 2.75, the rate of partial response was 60.5%, and the progression-free diseases was reported to be 22.7%.…”

Section: Selective Hepatic Arterial Embolizationmentioning

confidence: 99%

“…Other factors may be counted as lymph node involvement, invasion depth, presence of certain histologic markers, necrosis, high serum alkaline phosphatase level, advanced age, and WHO and TNM scoring systems. 16…”

Section: Tumor Classification and Grading Systems And Prognosismentioning

confidence: 99%

“…The sensitivity of helical multiphasic contrasted CT is over 80%, and even 100% sensitivity has been reported for tumors larger than 3 cm. 16,17 A typical pancreatic CT scan consists of the noncontrasted phase, contrasted arterial phase, and portal venous phase. 18 The advantageous aspects of MRI may include nonexposure to ionized radiation and excellent soft tissue contrast resonance.…”

Section: Ct and Mrimentioning

confidence: 99%

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Nonfunctional Pancreatic Neuroendocrine Tumors: Advances in Diagnosis, Management, and Controversies

Dumlu

Karakoç

Özdemir

2015

International Surgery

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In this article, we aimed to review the literature on the clinics and management of nonfunctional pancreatic neuroendocrine tumors (NPNET). Pancreatic neuroendocrine tumors (PNET) are rare tumors with a <1/100,000 incidence and constitute approximately 2 to 10% of all pancreatic tumors. Nonfunctional PNETs are difficult to detect at early stages since they have no symptoms. Except those detected accidentally during different diagnoses, the majority of PNETs are detected in the advanced stages, with symptoms related to tumor size or liver metastasis. We reviewed the studies published in the English medical literature through PubMed and summarized the clinical features and current approaches to the treatment and follow-up of the NPNET. The common imaging techniques used for the detection of tumor localization, size, locoregional, and metastatic involvement are contrasted computed tomography, magnetic resonance imaging, endoscopic ultrasonography, and somatostatin receptor scintigraphy. Surgical resection is the only curative treatment. However, in advanced locoregional disease and liver metastasis, interventive ablative therapies such as palliative reductive surgery, selective hepatic arterial embolization, radiofrequency ablation; and systemic therapies, such as peptide receptor radionuclide therapy, chemotherapy, somatostatin analogous therapy, interferon, VEGF inhibitor, and mTOR inhibitor may be used as symptom relieving or may improve progression-free survival and total survival. Current knowledge on NPNET shows that the treatment should be personalized considering the prognostic features and life expectancy of the patient.

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“…Over the past years, advances have been made in understanding the biology and clinical behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a heterogeneous group of tumors arising from the diffuse neuroendocrine system (Oberg 2012, Muniraj et al 2013. The estimated annual incidence of NETs in the USA increased 6.4-fold between 1973 and 2012, with an incidence rate of 3.56/100,000 in gastroenteropancreatic sites (Dasari et al 2017).…”

Section: Introductionmentioning

confidence: 99%

The IGF pathway is activated in insulinomas but downregulated in metastatic disease

Henfling¹,

Perren²,

Schmitt³

et al. 2018

Endocrine-Related Cancer

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Clinical and molecular studies have implicated epidermal growth factor receptor (EGFR), insulin-like growth factor (IGF) and target of rapamycin (mTOR) signaling pathways in the regulation of pancreatic neuroendocrine tumor (PanNET) growth. Interpretation and comparison of these studies is complex due to clinical and molecular tumor heterogeneity. We therefore focused in this study on insulinomas, which we examined for mRNA and protein expression of EGFR, IGF and mTOR signaling pathway components by quantitative real-time PCR (n=48) and immunohistochemistry (n=86). Findings were compared with normal pancreatic islets and correlated with histopathological data and clinical outcome. Insulinomas showed low EGFR and high IGF2 expression. IGFBP2, IGFBP3 and IGFBP6 mRNA levels were 2-4 folds higher than in islets. High protein expression of IGF2, IGF1R and INSR (in 51-92% of the tumors) and low to moderate expression of mTORC1 pathway proteins p-PS6k and p-4EBP1 (7-28% of the tumors) were observed. Correlations were found between 1) ERK1 mRNA expression and that of numerous IGF pathway genes, 2) p-ERK and IGF1R protein expression and 3) decrease of IGF pathway components and both metastatic disease and shorter 10 years disease free survival. In conclusion, our observations suggest that high expression of IGF signaling pathway components is a hallmark of insulinomas, but does not necessarily lead to increased mTOR signaling. Reduced expression of IGF pathway components may be an adverse prognostic factor in insulinomas.

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Pancreatic neuroendocrine tumors

Cited by 25 publications

References 96 publications

An unusual case of malignancy-related hypercalcemia

An unusual case of malignancy-related hypercalcemia

Nonfunctional Pancreatic Neuroendocrine Tumors: Advances in Diagnosis, Management, and Controversies

The IGF pathway is activated in insulinomas but downregulated in metastatic disease

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